ArticleAmerican journal of physiology. Heart and circulatory physiology2013
SOCS3 promotor hypermethylation and STAT3-NF-κB interaction downregulate SOCS3 expression in human coronary artery smooth muscle cells.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- IL-1β-induced STAT3 activation drives IL-17-producing CD8Journal of translational medicine · 2025Article
- Hybrid Receptor-Mediated Molecular Delineations in TNF-α and IGF-1-Induced Costimulatory Effects.International journal of molecular sciences · 2025Article
- JAK2/STAT3 Signaling Pathway Modulates Acute Methylmercury Toxicity in the Mouse Astrocyte C8-D1A Cell Line.Neurochemical research · 2025Article
- PD-1/PD-L1 inhibitor treatment associated with cardiotoxicity regulated by macrophage polarization and SOCS3/JAK/STAT3 signaling pathway.Central-European journal of immunology · 2025Article
- Role of the suppressor of cytokine signaling-3 in the pathogenesis of Graves' orbitopathy.Frontiers in endocrinology · 2025Article
- The Exacerbating Effects of the Tumor Necrosis Factor in Cardiovascular Stenosis: Intimal Hyperplasia.Cancers · 2024Review
- DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.Nature communications · 2023Article
- Increased Expression of Long Noncoding RNA LOC100506314 in T cells from Patients with Nonsegmental Vitiligo and Its Contribution to Vitiligo Pathogenesis.Mediators of inflammation · 2023Article
- Short communication: TNF-α and IGF-1 regulates epigenetic mechanisms of HDAC2 and HDAC10.PloS one · 2022Article
- The JAK/STAT signaling pathway: from bench to clinic.Signal transduction and targeted therapy · 2021Review
- Comprehensive analysis of suppressor of cytokine signaling proteins in human breast Cancer.BMC cancer · 2021Article
- Genetic information from discordant sibling pairs points to ESRP2 as a candidate trans-acting regulator of the CF modifier gene SCNN1B.Scientific reports · 2020Article
- Tumor Necrosis Factor α Influences Phenotypic Plasticity and Promotes Epigenetic Changes in Human Basal Forebrain Cholinergic Neuroblasts.International journal of molecular sciences · 2020Article
- The long non-coding RNA DANCR regulates the inflammatory phenotype of breast cancer cells and promotes breast cancer progression via EZH2-dependent suppression of SOCS3 transcription.Molecular oncology · 2020Article
- Visceral Adipose Tissue Inflammatory Factors (TNF-Alpha, SOCS3) in Gestational Diabetes (GDM): Epigenetics as a Clue in GDM Pathophysiology.International journal of molecular sciences · 2020Article
- Potential Molecular Mechanism of theBioMed research international · 2020Article
- Influenza Virus-Induced Robust Expression of SOCS3 Contributes to Excessive Production of IL-6.Frontiers in immunology · 2019Article
- Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction.Neural regeneration research · 2018Article
- Epigenetics of Mucus Hypersecretion in Chronic Respiratory Diseases.American journal of respiratory cell and molecular biology · 2018Review
- TNFR2 Stimulation Promotes Mitochondrial Fusion via Stat3- and NF-kB-Dependent Activation of OPA1 Expression.Circulation research · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Suppressor of cytokine signaling-3 (SOCS3) is an intracellular negative regulator of cytokine signaling pathway. We recently found significant reduction in SOCS3 expression in coronary artery smooth muscle cells (CASMCs) of atherosclerotic swine and also in vitro cultured cells. Here, we investigated the underlying mechanisms of SOCS3 downregulation by IGF-1 and TNF-α in human CASMCs(hCASMCs). We propose that hypermethylation of CpG islands in the SOCS3 promoter is responsible for decrease in SOCS3 expression involving STAT3 and NFkB-p65 interaction. Western blot and qPCR data revealed significant upregulation of SOCS3 (6- to 10-fold) in hCASMC when treated individually with TNF-α (100 ng/ml) or IGF-1 (100 ng/ml). However, a significant decrease (5-fold) was observed by the combined treatment with TNF-α and IGF-1 compared with individual stimulation. IGF-1 phosphorylated STAT3 and TNF-α-activated NF-κB in hCASMCs. In the nuclear extract of hCASMCs stimulated with both TNF-α and IGF-1, there was an interaction between NF-κB-p65 and pSTAT3, as determined by co-immunoprecipitation. Knockdown of STAT3 by small interfering RNA abolished SOCS3 expression in response to IGF-1. Methylation-specific PCR confirmed hypermethylation of SOCS3 promoter in hCASMCs stimulated with both TNF-α and IGF-1, and this was positively associated with elevated levels of DNA methyltransferase-I (9- to 10-fold). Knockdown of DNMT1 increased SOCS3 expression in IGF-1+TNF-α-stimulated cells. Downregulation of SOCS3 in the presence of both TNF-α and IGF-1 in hCASMCs is due to SOCS3 promoter hypermethylation involving STAT3-NFkBp65 interaction. Because TNF-α and IGF-1 are released due to mechanical injury during coronary intervention, hypermethylation of SOCS3 gene could be an underlying mechanism of intimal hyperplasia and restenosis.
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